Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

Active induction of experimental allergic encephalomyelitis

Nature Protocols volume 1, pages 1810–1819 (2006)Cite this article

Abstract

This protocol details a method to actively induce experimental allergic encephalomyelitis (EAE), a widely used animal model for studies of multiple sclerosis. EAE is induced by stimulating T-cell-mediated immunity to myelin antigens. Active induction of EAE is accomplished by immunization with myelin antigens emulsified in adjuvant. This protocol focuses on induction of EAE in mice; however, the same principles apply to EAE induction in other species. EAE in rodents is manifested typically as ascending flaccid paralysis with inflammation targeting the spinal cord. However, more diverse clinical signs can occur in certain strain/antigen combinations in rodents and in other species, reflecting increased inflammation in the brain.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: (a) Examples of different clinical courses that can be observed during classic EAE.

Similar content being viewed by others

References

  1. Sospedra, M. & Martin, R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 23, 683–747 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Lucchinetti, C. et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Annu. Neurol. 47, 707–717 (2000).

    Article  CAS  Google Scholar 

  3. Campbell, I.L., Stalder, A.K., Akwa, Y., Pagenstecher, A. & Asensio, V.C. Transgenic models to study the actions of cytokines in the central nervous system. Neuroimmunomodulation 5, 126–135 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Matsushima, G.K. & Morell, P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol. 11, 107–116 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Ercolini, A.M. & Miller, S.D. Mechanisms of immunopathology in murine models of central nervous system demyelinating disease. J. Immunol. 176, 3293–3298 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Zamvil, S.S. & Steinman, L. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol. 8, 579–621 (1990).

    Article  CAS  PubMed  Google Scholar 

  7. Kuchroo, V.K. et al. T cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire. Annu. Rev. Immunol. 20, 101–123 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. Koritschoner, R.S. & Schweinburg, F. Induktion von Paralyse und Rückenmarksentzündung durch Immunisierung von Kaninchen mit menschlichem Rückenmarksgewebe. Z. Immunitätsf. Exp. Ther. 42, 217–283 (1925).

    Google Scholar 

  9. Rivers, T.M., Sprunt, D.H. & Berry, G.P. Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J. Exp. Med. 58, 39–53 (1933).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Paterson, P.Y. Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J. Exp. Med. 111, 119–133 (1960).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kabat, E.A., Wolf, A. & Bezer, A.E. The rapid production of acute disseminated encephalomyelitis in rhesus monkeys by injection of heterologous and homologous brain tissue with adjuvant. J. Exp. Med. 85, 117–129 (1947).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Levine, S. & Sowinski, R. Experimental allergic encephalomyelitis in inbred and outbred mice. J. Immunol. 110, 139–143 (1973).

    CAS  PubMed  Google Scholar 

  13. Martenson, R.E., Deibler, G.E. & Kies, M.W. Microheterogeneity of guinea pig myelin basic protein. J. Biol. Chem. 244, 4261–4267 (1969).

    CAS  PubMed  Google Scholar 

  14. Olitsky, P.K. & Tal, C. Acute disseminated encephalomyelitis produced in mice by brain proteolipid (Folch–Lees). Proc. Soc. Exp. Biol. Med. 79, 50–53 (1952).

    Article  CAS  PubMed  Google Scholar 

  15. Poduslo, S.E. Proteins and glycoproteins in plasma membranes and in the membrane lamellae produced by purified oligodendroglia in culture. Biochim. Biophys. Acta 728, 59–65 (1983).

    Article  CAS  PubMed  Google Scholar 

  16. Lebar, R. & Vincent, C. Tentative identification of a second central nervous system myelin membrane autoantigen (M2) by a biochemical comparison with the basic protein (BP). J. Neuroimmunol. 1, 367–389 (1981).

    Article  CAS  PubMed  Google Scholar 

  17. Linnington, C., Webb, M. & Woodhams, P.L. A novel myelin-associated glycoprotein defined by a mouse monoclonal antibody. J. Neuroimmunol. 6, 387–396 (1984).

    Article  CAS  PubMed  Google Scholar 

  18. Ben-Nun, A., Wekerle, H. & Cohen, I.R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol. 11, 195–199 (1981).

    Article  CAS  PubMed  Google Scholar 

  19. Zamvil, S. et al. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317, 355–358 (1985).

    Article  CAS  PubMed  Google Scholar 

  20. McDevitt, H.O., Perry, R. & Steinman, L.A. Monoclonal anti-Ia antibody therapy in animal models of autoimmune disease. Ciba Found. Symp. 129, 184–193 (1987).

    CAS  PubMed  Google Scholar 

  21. Seamons, A., Perchellet, A. & Goverman, J. Immune tolerance to myelin proteins. Immunol. Res. 28, 201–221 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Wekerle, H., Linnington, H., Lassmann, H. & Meyermann, R. Cellular immune reactivity within the CNS. Trends Neurosci. 9, 271–277 (1986).

    Article  Google Scholar 

  23. Hickey, W.F. Migration of hematogenous cells through the blood–brain barrier and the initiation of CNS inflammation. Brain Pathol. 1, 97–105 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Brabb, T. et al. In situ tolerance within the central nervous system as a mechanism for preventing autoimmunity. J. Exp. Med. 192, 871–880 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tompkins, S.M. et al. De novo central nervous system processing of myelin antigen is required for the initiation of experimental autoimmune encephalomyelitis. J. Immunol. 168, 4173–4183 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. McMahon, E.J., Bailey, S.L., Castenada, C.V., Waldner, H. & Miller, S.D. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat. Med. 11, 335–339 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Kawakami, N. et al. The activation status of neuroantigen-specific T cells in the target organ determines the clinical outcome of autoimmune encephalomyelitis. J. Exp. Med. 199, 185–197 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Raine, C. The lesion in multiple sclerosis and chronic relapsing experimental allergic encephalomyelitis: a structural comparison. in Multiple Sclerosis: Clinical and Pathogenetic Basis (eds. Raine, C.S., McFarland, H.F. & Tourtellotte, W.W.) 243–286 (Chapman & Hall, Londan, 1997).

    Google Scholar 

  29. Stromnes, I.M. & Goverman, J.M. Passive induction of experimental allergic encephalomyelitis. Nat. Protocols doi 10.1038/nprot.2006.284 (2006).

  30. Sobel, R.A. Genetic and epigenetic influence on EAE phenotypes induced with different encephalitogenic peptides. J. Neuroimmunol. 108, 45–52 (2000).

    Article  CAS  PubMed  Google Scholar 

  31. Berger, T. et al. Experimental autoimmune encephalomyelitis: the antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system. Lab Invest. 76, 355–364 (1997).

    CAS  PubMed  Google Scholar 

  32. Linington, C., Bradl, M., Lassmann, H., Brunner, C. & Vass, K. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am. J. Pathol. 130, 443–454 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Waksman, B.H. & Adams, R.D. A comparative study of experimental allergic neuritis in the rabbit, guinea pig, and mouse. J. Neuropathol. Exp. Neurol. 15, 293–334 (1956).

    Article  CAS  PubMed  Google Scholar 

  34. Waksman, B.H. The distribution of experimental auto-allergic lesions. Its relation to the distribution of small veins. Am. J. Pathol. 37, 673–693 (1960).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Rose, L.M., Richards, T. & Alvord, E.C., Jr. Experimental allergic encephalomyelitis (EAE) in nonhuman primates: a model of multiple sclerosis. Lab. Anim. Sci. 44, 508–512 (1994).

    CAS  PubMed  Google Scholar 

  36. Genain, C.P. & Hauser, S.L. Experimental allergic encephalomyelitis in the New World monkey Callithrix jacchus. Immunol. Rev. 183, 159–172 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. t Hart, B.A. et al. Modelling of multiple sclerosis: lessons learned in a non-human primate. Lancet Neurol. 3, 588–597 (2004).

    Article  Google Scholar 

  38. Lebar, R., Boutry, J.M., Vincent, C., Robineaux, R. & Voisin, G.A. Studies on autoimmune encephalomyelitis in the guinea pig. II. An in vitro investigation on the nature, properties, and specificity of the serum-demyelinating factor. J. Immunol. 116, 1439–1446 (1976).

    CAS  PubMed  Google Scholar 

  39. Genain, C.P. et al. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate 96, 2966–2974 (1995).

  40. Schluesener, H.J., Sobel, R.A., Linington, C. & Weiner, H.L. A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J. Immunol. 139, 4016–4021 (1987).

    CAS  PubMed  Google Scholar 

  41. Adelmann, M. et al. The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. J. Neuroimmunol. 63, 17–27 (1995).

    Article  CAS  PubMed  Google Scholar 

  42. Stefferl, A. et al. Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the “resistant” Brown Norway rat: disease susceptibility is determined by MHC and MHC-linked effects on the B cell response. J. Immunol. 163, 40–49 (1999).

    CAS  PubMed  Google Scholar 

  43. Iglesias, A., Bauer, J., Litzenburger, T., Schubart, A. & Linington, C. T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36, 220–234 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Morris-Downes, M.M. et al. Pathological and regulatory effects of anti-myelin antibodies in experimental allergic encephalomyelitis in mice. J. Neuroimmunol. 125, 114–124 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Abdul-Majid, K.B. et al. Fc receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis. Scand. J. Immunol. 55, 70–81 (2002).

    Article  CAS  PubMed  Google Scholar 

  46. Oliver, A.R., Lyon, G.M. & Ruddle, N.H. Rat and human myelin oligodendrocyte glycoproteins induce experimental autoimmune encephalomyelitis by different mechanisms in C57BL/6 mice. J. Immunol. 171, 462–468 (2003).

    Article  CAS  PubMed  Google Scholar 

  47. Tsunoda, I., Kuang, L.Q., Theil, D.J. & Fujinami, R.S. Antibody association with a novel model for primary progressive multiple sclerosis: induction of relapsing-remitting and progressive forms of EAE in H2s mouse strains. Brain Pathol. 10, 402–418 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Haase, C.G. et al. The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls. J. Neuroimmunol. 114, 220–225 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. O'Connor, K.C. et al. Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. J. Immunol. 175, 1974–1982 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Storch, M.K. et al. Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol. 8, 681–694 (1998).

    Article  CAS  PubMed  Google Scholar 

  51. Butterfield, R.J. et al. Identification of genetic loci controlling the characteristics and severity of brain and spinal cord lesions in experimental allergic encephalomyelitis. Am. J. Pathol. 157, 637–645 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Encinas, J.A. & Kuchroo, V.K. Mapping and identification of autoimmunity genes. Curr. Opin. Immunol. 12, 691–697 (2000).

    Article  CAS  PubMed  Google Scholar 

  53. Becanovic, K., Jagodic, M., Wallstrom, E. & Olsson, T. Current gene-mapping strategies in experimental models of multiple sclerosis. Scand. J. Immunol. 60, 39–51 (2004).

    Article  CAS  PubMed  Google Scholar 

  54. Brabb, T. et al. Triggers of autoimmune disease in a murine T-cell receptor transgenic model for multiple sclerosis. J. Immunol. 159, 497–507 (1997).

    CAS  PubMed  Google Scholar 

  55. Teuscher, C. et al. Gender, age, and season at immunization uniquely influence the genetic control of susceptibility to histopathological lesions and clinical signs of experimental allergic encephalomyelitis: implications for the genetics of multiple sclerosis. Am. J. Pathol. 165, 1593–1602 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Levine, S., Wenk, E.J., Devlin, H.B., Pieroni, R.E. & Levine, L. Hyperacute allergic encephalomyelitis: adjuvant effect of pertussis vaccines and extracts. J. Immunol. 97, 363–368 (1966).

    CAS  PubMed  Google Scholar 

  57. Smith, M.E., Eller, N.L., McFarland, H.F., Racke, M.K. & Raine, C.S. Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple sclerosis. Am. J. Pathol. 155, 1147–1161 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Maatta, J.A., Nygardas, P.T. & Hinkkanen, A.E. Enhancement of experimental autoimmune encephalomyelitis severity by ultrasound emulsification of antigen/adjuvant in distinct strains of mice. Scand. J. Immunol. 51, 87–90 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. Fillmore, P.D. et al. Genetic analysis of the influence of neuroantigen-complete Freund's adjuvant emulsion structures on the sexual dimorphism and susceptibility to experimental allergic encephalomyelitis. Am. J. Pathol. 163, 1623–1632 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sakuma, H. et al. Clinicopathological study of a myelin oligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1 rats. Brain 127, 2201–2213 (2004).

    Article  PubMed  Google Scholar 

  61. Muller, D.M., Pender, M.P. & Greer, J.M. A neuropathological analysis of experimental autoimmune encephalomyelitis with predominant brain stem and cerebellar involvement and differences between active and passive induction. Acta Neuropathol. (Berl.) 100, 174–182 (2000).

    Article  CAS  Google Scholar 

  62. Bettelli, E. et al. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J. Exp. Med. 197, 1073–1081 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Huseby, E.S. et al. A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J. Exp. Med. 194, 669–676 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Krakowski, M. & Owens, T. Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur. J. Immunol. 26, 1641–1646 (1996).

    Article  CAS  PubMed  Google Scholar 

  65. Willenborg, D.O., Fordham, S., Bernard, C.C., Cowden, W.B. & Ramshaw, I.A. IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J. Immunol. 157, 3223–3227 (1996).

    CAS  PubMed  Google Scholar 

  66. Abromson-Leeman, S. et al. T-cell properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis. Am. J. Pathol. 165, 1519–1533 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wensky, A.K. et al. IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitis. J. Immunol. 174, 1416–1423 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Engelhardt, B. & Ransohoff, R.M. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 26, 485–495 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. Weiner, H.L. et al. Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu. Rev. Immunol. 12P809-37, 809–837 (1994).

    Article  Google Scholar 

  70. Furtado, G.C. et al. Regulatory T cells in spontaneous autoimmune encephalomyelitis. Immunol. Rev. 182, 122–134 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Sewell, D.L., Reinke, E.K., Hogan, L.H., Sandor, M. & Fabry, Z. Immunoregulation of CNS autoimmunity by helminth and mycobacterial infections. Immunol. Lett. 82, 101–110 (2002).

    Article  CAS  PubMed  Google Scholar 

  72. Kohm, A.P., Carpentier, P.A. & Miller, S.D. Regulation of experimental autoimmune encephalomyelitis (EAE) by CD4+CD25+ regulatory T cells. Novartis Found. Symp. 252, 45–52 discussion 52–44, 106–114 (2003).

    CAS  PubMed  Google Scholar 

  73. Whitacre, C.C. et al. Regulation of autoreactive T cell function by oral tolerance to self-antigens. Ann. NY Acad. Sci. 1029, 172–179 (2004).

    Article  CAS  PubMed  Google Scholar 

  74. Sriram, S. & Steiner, I. Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis. Ann. Neurol. 58, 939–945 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Steinman, L. & Zamvil, S.S. How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis. Ann. Neurol. 60, 12–21 (2006).

    Article  CAS  PubMed  Google Scholar 

  76. Friese, M.A. et al. The value of animal models for drug development in multiple sclerosis. Brain 129, 1940–1952 (2006).

    Article  PubMed  Google Scholar 

  77. Goverman, J. et al. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72, 551–560 (1993).

    Article  CAS  PubMed  Google Scholar 

  78. Lafaille, J.J., Nagashima, K., Katsuki, M. & Tonegawa, S. High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice. Cell 78, 399–408 (1994).

    Article  CAS  PubMed  Google Scholar 

  79. Liu, G.Y. et al. Low avidity recognition of self-antigen by T cells permits escape from central tolerance. Immunity 3, 407–415 (1995).

    Article  CAS  PubMed  Google Scholar 

  80. Waldner, H., Whitters, M.J., Sobel, R.A., Collins, M. & Kuchroo, V.K. Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor 97, 3412–3417 (2000).

  81. Zhou, S.R., Moscarello, M.A. & Whitaker, J.N. The effects of citrullination or variable amino-terminus acylation on the encephalitogenicity of human myelin basic protein in the PL/J mouse. J. Neuroimmunol. 62, 147–152 (1995).

    Article  CAS  PubMed  Google Scholar 

  82. Nicholas, A.P., Sambandam, T., Echols, J.D. & Barnum, S.R. Expression of citrullinated proteins in murine experimental autoimmune encephalomyelitis. J. Comp. Neurol. 486, 254–266 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Raijmakers, R. et al. Citrullination of central nervous system proteins during the development of experimental autoimmune encephalomyelitis. J. Comp. Neurol. 486, 243–253 (2005).

    Article  PubMed  Google Scholar 

  84. Lassmann, H. & Ransohoff, R.M. The CD4-Th1 model for multiple sclerosis: a crucial re-appraisal. Trends Immunol. 25, 132–137 (2004).

    Article  CAS  PubMed  Google Scholar 

  85. Goverman, J., Perchellet, A. & Huseby, E.S. The role of CD8(+) T cells in multiple sclerosis and its animal models. Curr. Drug Targets Inflamm. Allergy 4, 239–245 (2005).

    Article  CAS  PubMed  Google Scholar 

  86. Friese, M.A. & Fugger, L. Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain 128, 1747–1763 (2005).

    Article  PubMed  Google Scholar 

  87. McDole, J., Johnson, A.J. & Pirko, I. The role of CD8+ T-cells in lesion formation and axonal dysfunction in multiple sclerosis. Neurol. Res. 28, 256–261 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Sun, D. et al. Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice. J. Immunol. 166, 7579–7587 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Ford, M.L. & Evavold, B.D. Specificity, magnitude, and kinetics of MOG-specific CD8+ T cell responses during experimental autoimmune encephalomyelitis. Eur. J. Immunol. 35, 76–85 (2005).

    Article  CAS  PubMed  Google Scholar 

  90. Huseby, E.S., Ohlen, C. & Goverman, J. Cutting edge: myelin basic protein-specific cytotoxic T cell tolerance is maintained in vivo by a single dominant epitope in H-2k mice. J. Immunol. 163, 1115–1118 (1999).

    CAS  PubMed  Google Scholar 

  91. Amor, S. et al. Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. J. Immunol. 153, 4349–4356 (1994).

    CAS  PubMed  Google Scholar 

  92. Elliott, E.A. et al. Treatment of experimental encephalomyelitis with a novel chimeric fusion protein of myelin basic protein and proteolipid protein. J. Clin. Invest. 98, 1602–1612 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lublin, F.D. Delayed, relapsing experimental allergic encephalomyelitis in mice. Role of adjuvants and pertussis vaccine. J. Neurol. Sci. 57, 105–110 (1982).

    Article  CAS  PubMed  Google Scholar 

  94. Tsunoda, I. et al. Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA. Brain Pathol. 9, 481–493 (1999).

    Article  CAS  PubMed  Google Scholar 

  95. Segal, B.M., Chang, J.T. & Shevach, E.M. CpG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo. J. Immunol. 164, 5683–5688 (2000).

    Article  CAS  PubMed  Google Scholar 

  96. Lorentzen, J.C. et al. Protracted, relapsing and demyelinating experimental autoimmune encephalomyelitis in DA rats immunized with syngeneic spinal cord and incomplete Freund's adjuvant. J. Neuroimmunol. 63, 193–205 (1995).

    Article  CAS  PubMed  Google Scholar 

  97. Lenz, D.C., Wolf, N.A. & Swanborg, R.H. Strain variation in autoimmunity: attempted tolerization of DA rats results in the induction of experimental autoimmune encephalomyelitis. J. Immunol. 163, 1763–1768 (1999).

    CAS  PubMed  Google Scholar 

  98. Stosic-Grujicic, S., Ramic, Z., Bumbasirevic, V., Harhaji, L. & Mostarica-Stojkovic, M. Induction of experimental autoimmune encephalomyelitis in Dark Agouti rats without adjuvant. Clin. Exp. Immunol. 136, 49–55 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Driscoll, B.F., Kies, M.W. & Alvord, E.C., Jr. Protection against experimental allergic encephalomyelitis with peptides derived from myelin basic protein: presence of intact encephalitogenic site is essential. J. Immunol. 117, 110–114 (1976).

    CAS  PubMed  Google Scholar 

  100. O'Neill, J.K., Baker, D. & Turk, J.L. Inhibition of chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse. J. Neuroimmunol. 41, 177–187 (1992).

    Article  CAS  PubMed  Google Scholar 

  101. Marusic, S. & Tonegawa, S. Tolerance induction and autoimmune encephalomyelitis amelioration after administration of myelin basic protein-derived peptide. J. Exp. Med. 186, 507–515 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bernard, C.C. & Carnegie, P.R. Experimental autoimmune encephalomyelitis in mice: immunologic response to mouse spinal cord and myelin basic proteins. J. Immunol. 114, 1537–1540 (1975).

    CAS  PubMed  Google Scholar 

  103. Donovan, J. & Brown, P. Anesthesia. In Current Protocols in Immunology Vol. 1 (eds. Coligan, J.E., Kruisbeek, A.M., Margulies, D.H., Shevach, E.M. & Strober, W.) 1.4.1–1.4.5 (John Wiley & Sons, Hoboken, 1994).

    Google Scholar 

  104. Hedenqvist, P. & Hellebrekers, L.J. Laboratory animal analgesia, anesthesia, and euthanasia. in Handbook of Laboratory Animal Science: Essential Principles and Practices 2nd edn., 2 Vol. 1 (eds. Hau, J. & van Hoosier, G.L., Jr.) 413–455 (CRC Press, Boca Raton, FL, 2003).

    Google Scholar 

  105. Otto, K. Anesthesia, analgesia and euthanasia. In The Laboratory Mouse (eds. Hedrich, H. & Bullock, G.) 555–569 (Elsevier Academic Press, Amsterdam, 2004).

    Chapter  Google Scholar 

  106. Cooper, H.M. & Patterson, Y. Production of antibodies. In Current Protocols in Immunology Vol. 1 (eds. Coligan, J.E., Kruisbeek, A.M., Margulies, D.H., Shevach, E.M. & Strober, W.) 2.4.1–2.4.9 (John Wiley & Sons, Hoboken, 1994).

    Google Scholar 

  107. Bischof, F. et al. A structurally available encephalitogenic epitope of myelin oligodendrocyte glycoprotein specifically induces a diversified pathogenic autoimmune response. J. Immunol. 173, 600–606 (2004).

    Article  CAS  PubMed  Google Scholar 

  108. Matejuk, A., Hopke, C., Vandenbark, A.A., Hurn, P.D. & Offner, H. Middle-age male mice have increased severity of experimental autoimmune encephalomyelitis and are unresponsive to testosterone therapy. J. Immunol. 174, 2387–2395 (2005).

    Article  CAS  PubMed  Google Scholar 

  109. Begolka, W.S., Vanderlugt, C.L., Rahbe, S.M. & Miller, S.D. Differential expression of inflammatory cytokines parallels progression of central nervous system pathology in two clinically distinct models of multiple sclerosis. J. Immunol. 161, 4437–4446 (1998).

    CAS  PubMed  Google Scholar 

  110. Hofstetter, H.H. et al. Does the frequency and avidity spectrum of the neuroantigen-specific T cells in the blood mirror the autoimmune process in the central nervous system of mice undergoing experimental allergic encephalomyelitis? J. Immunol. 174, 4598–4605 (2005).

    Article  CAS  PubMed  Google Scholar 

  111. Lehmann, P.V., Sercarz, E.E., Forsthuber, T., Dayan, C.M. & Gammon, G. Determinant spreading and the dynamics of the autoimmune T-cell repertoire. Immunol. Today 14, 203–208 (1993).

    Article  CAS  PubMed  Google Scholar 

  112. Tuohy, V.K., Fritz, R.B. & Ben-Nun, A. Self-determinants in autoimmune demyelinating disease: changes in T-cell response specificity. Curr. Opin. Immunol. 6, 887–891 (1994).

    Article  CAS  PubMed  Google Scholar 

  113. Miller, S.D. & Eagar, T.N. Functional role of epitope spreading in the chronic pathogenesis of autoimmune and virus-induced demyelinating diseases. Adv. Exp. Med. Biol. 490, 99–107 (2001).

    Article  CAS  PubMed  Google Scholar 

  114. Zamvil, S.S. et al. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324, 258–260 (1986).

    Article  CAS  PubMed  Google Scholar 

  115. Urban, J.L. et al. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 54, 577–592 (1988).

    Article  CAS  PubMed  Google Scholar 

  116. Tuohy, V.K., Lu, Z., Sobel, R.A., Laursen, R.A. & Lees, M.B. Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice. J. Immunol. 142, 1523–1527 (1989).

    CAS  PubMed  Google Scholar 

  117. Greer, J.M., Kuchroo, V.K., Sobel, R.A. & Lees, M.B. Identification and characterization of a second encephalitogenic determinant of myelin proteolipid protein (residues 178–191) for SJL mice. J. Immunol. 149, 783–788 (1992).

    CAS  PubMed  Google Scholar 

  118. Kono, D.H. et al. Two minor determinants of myelin basic protein induce experimental allergic encephalomyelitis in SJL/J mice. J. Exp. Med. 168, 213–227 (1988).

    Article  CAS  PubMed  Google Scholar 

  119. Fritz, R.B. & McFarlin, D.E. Encephalitogenic epitopes of myelin basic protein. Chem. Immunol. 46, 101–125 (1989).

    Article  CAS  PubMed  Google Scholar 

  120. Sakai, K. et al. Prevention of experimental encephalomyelitis with peptides that block interaction of T cells with major histocompatibility complex proteins. Proc. Natl. Acad. Sci. USA 86, 9470–9474 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. McRae, B.L., Vanderlugt, C.L., Dal Canto, M.C. & Miller, S.D. Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J. Exp. Med. 182, 75–85 (1995).

    Article  CAS  PubMed  Google Scholar 

  122. Mendel, I., Kerlero de Rosbo, N. & Ben-Nun, A. A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: fine specificity and T cell receptor V beta expression of encephalitogenic T cells. Eur. J. Immunol. 25, 1951–1959 (1995).

    Article  CAS  PubMed  Google Scholar 

  123. Maron, R. et al. Genetic susceptibility or resistance to autoimmune encephalomyelitis in MHC congenic mice is associated with differential production of pro- and anti-inflammatory cytokines. Int. Immunol. 11, 1573–1580 (1999).

    Article  CAS  PubMed  Google Scholar 

  124. Amor, S., Baker, D., Groome, N. & Turk, J.L. Identification of a major encephalitogenic epitope of proteolipid protein (residues 56–70) for the induction of experimental allergic encephalomyelitis in Biozzi AB/H and nonobese diabetic mice. J. Immunol. 150, 5666–5672 (1993).

    CAS  PubMed  Google Scholar 

  125. Amor, S. et al. Encephalitogenic epitopes of myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein for experimental allergic encephalomyelitis induction in Biozzi ABH (H-2Ag7) mice share an amino acid motif. J. Immunol. 156, 3000–3008 (1996).

    CAS  PubMed  Google Scholar 

  126. Smith, P.A. et al. Epitope spread is not critical for the relapse and progression of MOG 8-21 induced EAE in Biozzi ABH mice. J. Neuroimmunol. 164, 76–84 (2005).

    Article  CAS  PubMed  Google Scholar 

  127. Greer, J.M. et al. Immunogenic and encephalitogenic epitope clusters of myelin proteolipid protein. J. Immunol. 156, 371–379 (1996).

    CAS  PubMed  Google Scholar 

  128. Abdul-Majid, K.B. et al. Screening of several H-2 congenic mouse strains identified H-2(q) mice as highly susceptible to MOG-induced EAE with minimal adjuvant requirement. J. Neuroimmunol. 111, 23–33 (2000).

    Article  CAS  PubMed  Google Scholar 

  129. Cua, D.J., Hinton, D.R. & Stohlman, S.A. Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. J. Immunol. 155, 4052–4059 (1995).

    CAS  PubMed  Google Scholar 

  130. Voskuhl, R.R., Pitchekian-Halabi, H., MacKenzie-Graham, A., McFarland, H.F. & Raine, C.S. Gender differences in autoimmune demyelination in the mouse: implications for multiple sclerosis. Ann. Neurol. 39, 724–733 (1996).

    Article  CAS  PubMed  Google Scholar 

  131. Bebo, B.F., Jr. et al. Gonadal hormones influence the immune response to PLP 139-151 and the clinical course of relapsing experimental autoimmune encephalomyelitis. J. Neuroimmunol. 84, 122–130 (1998).

    Article  CAS  PubMed  Google Scholar 

  132. Papenfuss, T.L. et al. Sex differences in experimental autoimmune encephalomyelitis in multiple murine strains. J. Neuroimmunol. 150, 59–69 (2004).

    Article  CAS  PubMed  Google Scholar 

  133. Reddy, J. et al. Cutting edge: CD4+CD25+ regulatory T cells contribute to gender differences in susceptibility to experimental autoimmune encephalomyelitis. J. Immunol. 175, 5591–5595 (2005).

    Article  CAS  PubMed  Google Scholar 

  134. Mendel Kerlero de Rosbo, N. & Ben-Nun, A. Delineation of the minimal encephalitogenic epitope within the immunodominant region of myelin oligodendrocyte glycoprotein: diverse V beta gene usage by T cells recognizing the core epitope encephalitogenic for T cell receptor V beta b and T cell receptor V beta a H-2b mice. Eur. J. Immunol. 26, 2470–2479 (1996).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge Dr. Thea Brabb and Hannah S. Simkins for critical reading of the manuscript, and Hannah S. Simkins for help with manuscript preparation.

Author information

Authors and Affiliations

  1. Department of Immunology, University of Washington, Box 357650, 1959 NE Pacific Street, Seattle, 98195-7650, Washington, USA

    Ingunn M Stromnes & Joan M Goverman

Authors
  1. Ingunn M Stromnes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joan M Goverman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joan M Goverman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stromnes, I., Goverman, J. Active induction of experimental allergic encephalomyelitis. Nat Protoc 1, 1810–1819 (2006). https://doi.org/10.1038/nprot.2006.285

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2006.285

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing